About

Translating our scientific discoveries into novel precision treatment options and immunotherapies to prevent and treat cancer.

Research topics

• Biology
• Cancer research
• Genetics
• Internal medicine
• Cell biology
• Medicine
• Oncology
• Surgery
• Pathology
• Immunology

Selected publications

• Supplementary Table S1 from A Randomized Multi-institutional Phase II Trial of Everolimus as Adjuvant Therapy in Patients with Locally Advanced Squamous Cell Cancer of the Head and Neck

  2025-11-25

  articleOpen access

  <p>List of all observed somatic mutations in TP53.</p>

  PublisherDOI

• Figure S1 from Genome-Wide CRISPR Screening Reveals That mTOR Inhibition Initiates Ferritinophagy and Ferroptosis in Head and Neck Cancer

  2025-08-15

  preprintOpen accessSenior author

  <p>Genome-wide CRISPR screening identified inhibition of the Autophagy pathway as the mechanism of mTORi resistance in HNSCC. (Related to Figure 1)</p>

  PublisherDOI

• Aberrant Hippo-YAP/TEAD signaling drives malignant transcriptional reprogramming in external auditory canal squamous cell carcinoma

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-01

  preprintOpen access

  Abstract Purpose External auditory canal squamous cell carcinoma (EACSCC) is an extremely rare malignancy. The molecular characteristics and evidence-based therapeutic strategies of EACSCC still remain to be elucidated. Experimental Design Comprehensive analyses of RNA sequencing (RNA-seq) and ChIP sequencing (ChIP-seq) utilizing YAP and H3K27Ac antibodies were performed in primary EACSCC and noncancerous ear skin samples. Functional experiments were performed in EACSCC-derived cells and Head and Neck Squamous Cell Carcinoma (HNSCC) cells in vitro and in vivo . Immunohistochemical staining of primary EACSCC tissues as well as survival analysis were conducted. Results RNA-seq indicated hyperactivation of YAP/TEAD-mediated transcriptional programs in EACSCC. H3K27Ac ChIP-seq suggested gained accessibility for transcription factor (TF) binding sites for TEAD, AP-1 and PITX TFs in EACSCC, and presence of EACSCC-specific super enhancers (SEs). YAP-bound SEs were involved in oncogenic transcription, including EGFR signaling. Small molecule TEAD inhibitor (smTEADi) VT104 showed significant suppression of proliferation and clonogenicity in EACSCC cells. Importantly, smTEADi not only inhibited YAP-TEAD interaction but also induced YAP-PITX2 binding, suggesting that PITX2 could represent an alternative partner TF of YAP under TEAD-inhibited conditions. Knockdown of PITX2 inhibited cell growth and migration of EACSCC and HNSCC cells, whereas overexpression of PITX2 induced expression of cell cycle, stemness, and EMT genes, as well as YAP/TAZ-TEAD target genes, and promoted tumor growth in vivo . Nuclear YAP and PITX2 expression were significantly correlated with poor prognosis of EACSCC patients. Conclusions This study highlighted the hyperactivation of the YAP-TEAD/PITX2 transcriptional program and its potential as a therapeutic target in EACSCC. Translational Relevance External auditory canal squamous cell carcinoma (EACSCC) is an extremely rare malignancy related to chronic tissue damage and inflammation. Due to its rarity, the molecular characteristics of EACSCC are poorly understood, and evidence-based therapeutic strategies are not fully developed. Here, we provide evidence of hyperactivation of YAP/TEAD-driven transcriptional programs in EACSCC, utilizing comprehensive analyses of RNA-seq and YAP/H3K27Ac ChIP-seq in clinical tissue samples, as well as in vitro and in vivo experiments. In addition, our data suggest that the PITX2 transcription factor (TF) could represent an alternative partner TF of YAP under TEAD-inhibited conditions, which may rescue oncogenic transcription of TEAD. Importantly, YAP and PITX2 are co-expressed in EACSCC and predict poor prognosis of EACSCC patients. Our results provide a rationale for YAP-hyperactivation in EACSCC and contribute to a better understanding of this malignancy and the development of new therapeutic strategies.

  PublisherOA PDFDOI

• Figure S9 from Genome-Wide CRISPR Screening Reveals That mTOR Inhibition Initiates Ferritinophagy and Ferroptosis in Head and Neck Cancer

  2025-08-15

  articleOpen accessSenior author

  <p>mTORC1 is involved in the induction of ferroptosis and ferritinophagy. (Related to Figure 3)</p>

  PublisherDOI

• Table S1 from Genome-Wide CRISPR Screening Reveals That mTOR Inhibition Initiates Ferritinophagy and Ferroptosis in Head and Neck Cancer

  2025-08-15

  articleOpen accessSenior author

  <p>Resistance driving hits selected from CRISPR screening</p>

  PublisherOA PDFDOI

• Figure S15 from Genome-Wide CRISPR Screening Reveals That mTOR Inhibition Initiates Ferritinophagy and Ferroptosis in Head and Neck Cancer

  2025-08-15

  articleOpen accessSenior author

  <p>Combination therapy with mTORi and auranofin enhances ferroptosis. (Related to Figure 6)</p>

  PublisherDOI

• PROTACs in cancer immunotherapy: a minireview

  Biochemical Society Transactions · 2025-10-01

  articleOpen access

  The discovery of immune checkpoint blockade as a therapeutic strategy to induce immunogenic cancer cell elimination has shown great success in the treatment of various cancers. However, limited response rates highlight the need for further development in this field. Promising new preclinical developments include the discoveries of proteolysis-targeting chimeras (PROTACs) to interfere with tumor immune escape signaling. Pharmacological induction of targeted protein degradation by these chimeras has shown advantages in inhibiting non-enzymatic protein functions and difficult to target protein-protein interactions. Furthermore, the induced degradation was shown to promote changes in the major histocompatibility complex I ligandome, which can be leveraged for an immune stimulus, increasing the cancer immune response. In this minireview, we highlight the research efforts ongoing towards employing PROTACs in immunotherapy for cancer treatment. Specifically, we outline how the unique mechanism of action can be leveraged to enhance the immune response or inhibit immune suppression.

  PublisherOA PDFDOI

• Inhibition of anti-apoptotic BCL2 overcomes adaptive resistance to co-targeting of the protein kinase FAK and MEK in GNAQ-driven uveal melanoma

  Journal of Biological Chemistry · 2025-09-11 · 1 citations

  articleOpen accessSenior author

  Uveal melanoma (UVM) is the most common eye cancer in adults, with 50% of patients developing overt metastasis that often proves fatal. The majority of UVM harbor mutations in GNAQ or GNA11, encoding constitutively active Gαq proteins. Combined inhibition of MEK and FAK downstream of Gαq has shown promising effects in UVM cells by inducing apoptotic cell death, but resistance to this strategy can occur in the clinic. Here, we aimed to identify new targets to overcome resistance to MEK + FAK inhibition (FAKi + MEKi). Reverse-phase protein array (RPPA) analysis in UVM cells treated with FAKi + MEKi showed increased levels of pro-apoptotic proteins, such as PUMA and BIM, which promoted cell death. However, we observed an adaptive increase in anti-apoptotic proteins, including BCL2, upon FAK + MEK blockade. We generated UVM cells resistant to FAKi + MEKi by prolonged exposure. Whole-exome sequencing did not reveal relevant acquired mutations; instead, resistant cells exhibit increased BCL2 levels. Moreover, expression of a stable BCL2 mutant confers resistance to both FAKi + MEKi and FAKi+"RAF-MEK clamp" (avutometinib) treatment. Of direct translational relevance, we found that an approved BCL2 inhibitor (venetoclax) displays synergistic efficacy with FAK + MEK blockade and overcomes acquired resistance, including when combined with darovasertib, a dual PKC/PKN inhibitor limiting MEK and FAK signaling that is under clinical evaluation. Our findings suggest that resistance to FAKi + MEKi in UVM cells can be driven by an adaptive upregulation of the anti-apoptotic protein BCL2, and that, in turn, BCL2 inhibitors represent a promising precision-targeted strategy to overcome FAKi + MEKi treatment resistance and improve therapeutic outcomes.

  PublisherDOI

• Supplementary Table S3 from A Randomized Multi-institutional Phase II Trial of Everolimus as Adjuvant Therapy in Patients with Locally Advanced Squamous Cell Cancer of the Head and Neck

  2025-11-25

  articleOpen access

  <p>Adverse events at least possibly related to study drug by NIH-NCI Common Terminology Criteria for Adverse Events (CTCAE), version. 4.0.</p>

  PublisherDOI

• Supplementary Data from Mutated HRAS Activates YAP1–AXL Signaling to Drive Metastasis of Head and Neck Cancer

  2025-11-24

  articleOpen access

  <p>Supplementary Materials and Methods</p>

  PublisherDOI

Recent grants

• Targeting Signaling Vulnerabilities for Oral Cancer Prevention

  NIH · $4.7M · 2017–2027

• Signal Transduction by PI3K/mTOR

  NIH · $2.4M · 2021–2026

• Molecular Mechanisms Of Growth Control And Carcinogenesis

  NIH · $11.5M

• Oral Carcinogenesis

  NIH · $11.4M

• Co-targeting the HER3 oncogenic signaling circuitry and PD-1 as a novel multimodal precision immunotherapy for HNSCC

  NIH · $2.5M · 2019–2024

Frequent coauthors

• Vyomesh Patel

  Cancer Research Malaysia

  341 shared

• Alfredo Molinolo

  336 shared

• Zhiyong Wang

  China Academy of Space Technology

  188 shared

• Panomwat Amornphimoltham

  Walailak University

  178 shared

• Joseph A. Califano

  University of California, San Diego

  141 shared

• Daniel Martı́n

  National Institute on Deafness and Other Communication Disorders

  115 shared

• James F. Rusling

  Ollscoil na Gaillimhe – University of Galway

  104 shared

• Hidemi Teramoto

  Koujin Hospital

  95 shared

Labs

• Gutkind LabPI

  1-2 sentence research focus

Education

• Ph.D., Pharmacology

  University of California, San Diego

  2015

Awards & honors

• American Cancer Society (ACS) Research Professor Award
• Named Chair of the Department of Pharmacology
• Elected to the National Academy of Medicine (NAM)